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bioRxiv · 10.64898/2026.10.13.758074

cBAF drives AR-V7 expression through regulation of transcriptional termination in castration-resistant prostate cancer

Nakano, M.·Uzokboev, S.·Kirkland, J. G.·Tao, W. A.·Dykhuizen, E.
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Abstract

The androgen receptor splice variant AR-V7 drives resistance to androgen receptor-targeted therapies in castration-resistant prostate cancer (CRPC), but the mechanisms governing its expression remain incompletely understood. Here, we identify the canonical BAF (cBAF) chromatin remodeling complex as a selective regulator of AR-V7 expression. Pharmacologic and genetic disruption of cBAF reduced AR-V7 levels, suppressed AR-V7-dependent transcriptional programs, and impaired CRPC cell proliferation. Mechanistically, cBAF binds an intronic regulatory element downstream of AR cryptic exon 3, where it maintains chromatin accessibility, enhancer activity, and promoter-enhancer looping. cBAF loss decreases recruitment of transcription termination machinery, reduces RNA polymerase II Thr4 phosphorylation, and promotes transcriptional readthrough beyond the AR-V7 polyadenylation site. POINT-seq revealed that cBAF-dependent transcriptional termination is required for AR-V7 biogenesis and regulates termination at a subset of genes genome-wide. Together, these findings uncover a role for cBAF in chromatin-mediated control of transcriptional termination and establish this mechanism as a critical determinant of AR-V7 expression.

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Nakano, M., Uzokboev, S., Kirkland, J. G., Tao, W. A., Dykhuizen, E.. 2026-10-18. cBAF drives AR-V7 expression through regulation of transcriptional termination in castration-resistant prostate cancer. https://doi.org/10.64898/2026.10.13.758074

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